Fourth International Study of Infarct Survival - ISIS-4


Captopril, nitrates, and IV magnesium for short-term mortality in acute MI.


Captopril oral mononitrate and intravenous magnesium will decrease short-term mortality when given routinely early after acute myocardial infarction.

Study Design

Study Design:

Patients Screened: Not detailed
Patients Enrolled: 58,050
Mean Follow Up: 1 month

Patient Populations:

Acute myocardial infarction (< 24 hours)


Persistent hypotension
Cardiogenic shock

Primary Endpoints:

All cause mortality at 5 weeks

Secondary Endpoints:

Mortality of 12 months
Cardiovascular deaths
Development of heart failure

Drug/Procedures Used:

Captopril (6.25mg titrated to 50mg bid)
Oral mononitrate 30mg titrated to 60mg qd
Intravenous magnesium sulfate
All cause mortality at 5 weeks

Principal Findings:

7% proportional reduction in 5 week mortality in captopril group (p = 0.02)
Patients presenting with prior infarction or heart failure appeared to have greater benefit with captopril.
Survival advantage appeared maintained out to 12 months.
Mononitrate and magnesium seemingly had no impact on post infarction mortality.


In this post infarction study, intravenous magnesium was ineffective, and although oral nitrate therapy appeared to be safe, it did not produce a clear reduction in one month mortality. This study suggested that for a wide range of post infarction patients ACE inhibitor therapy started early prevents about five deaths per 1,000 in the first month (p = 0.006), with somewhat greater benefits in high-risk patients. The benefit from one month of early ACE inhibitor therapy seems to persist for the first year.


1. Lancet 1995;345:669-685. Final results

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Magnesium Sulfate, Myocardial Infarction, Infarction, Nitrates, Heart Failure, Captopril

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